dexlansoprazole and 5-hydroxylansoprazole

The purpose of this study was to elucidate the pharmacokinetics of each enantiomer of lansoprazole and 5-hydroxylansoprazole in three different CYP2C19 genotype groups of Japanese subjects.. Healthy subjects ( n=18), of whom 6 were homozygous extensive metabolizers (homEMs), 6 were heterozygous extensive metabolizers (hetEMs) and 6 were poor metabolizers (PMs), participated in the study. After a single oral dose of 60 mg of racemic lansoprazole, the plasma concentrations of the lansoprazole enantiomers, 5-hydroxylansoprazole enantiomers and lansoprazole sulfone were measured for 24 h post-dose.. The plasma concentrations of ( R)-lansoprazole were remarkably higher in all three CYP2C19 genotype groups than those of the corresponding ( S)-enantiomer. The mean maximum plasma concentration ( C(max)) of ( S)-lansoprazole differed significantly among the three groups, whereas there was no difference for the ( R)-enantiomer. The relative area under the plasma concentration (AUC) ratios of ( R)- and ( S)-lansoprazole in the homEMs, hetEMs, and PMs were 1:1.5:4.0 and 1:1.8:7.4, respectively. Yet, the relative AUC ratios of 5-hydroxylansoprazole to lansoprazole for the ( R)- and ( S)-enantiomers in the homEMs, hetEMs, and PMs were almost the same (1:0.73:0.12 and 1:0.77:0.13, respectively). However, the AUC ratios of the ( S)-enantiomer were 13-fold greater for the three CYP2C19 genotypes than those of the corresponding ( R)-enantiomer.. The magnitude of the contribution of CYP2C19 to the 5-hydroxylation of ( S)-lansoprazole was greater than that of the ( R)-enantiomer. The R/S ratios for the AUC of lansoprazole for the homEMs, hetEMs and PMs were 12.7, 8.5 and 5.8, respectively, suggesting a significant effect of CYP2C19 polymorphisms on the stereoselective disposition of lansoprazole.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Anti-Ulcer Agents; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C19; Dexlansoprazole; Female; Genotype; Half-Life; Humans; Lansoprazole; Male; Mixed Function Oxygenases; Omeprazole; Proton Pump Inhibitors; Stereoisomerism; Time Factors